Muntoni Francesco, Torelli Silvia, Ferlini Alessandra
Department of Paediatrics, Imperial College London, Hammersmith Hospital Campus, London, UK.
Lancet Neurol. 2003 Dec;2(12):731-40. doi: 10.1016/s1474-4422(03)00585-4.
A large and complex gene on the X chromosome encodes dystrophin. Many mutations have been described in this gene, most of which affect the expression of the muscle isoform, the best-known protein product of this locus. These mutations result in the Duchenne and Becker muscular dystrophies (DMD and BMD). However, there are several other tissue specific isoforms of dystrophin, some exclusively or predominantly expressed in the brain or the retina. Mutations affecting the correct expression of these tissue-specific isoforms have been associated with the CNS involvement common in DMD. Rare mutations also account for the allelic disorder X-linked dilated cardiomyopathy, in which dystrophin expression or function is affected mostly or exclusively in the heart. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has provided insights into several regulatory mechanisms governing the gene expression profile. Here, we focus on current understanding of the genotype-phenotype relation for mutations in the dystrophin gene and their implications for gene functions.
X染色体上一个庞大而复杂的基因编码抗肌萎缩蛋白。该基因已发现许多突变，其中大多数影响肌肉异构体的表达，这是该基因座最著名的蛋白质产物。这些突变导致杜兴氏和贝克氏肌营养不良症（DMD和BMD）。然而，抗肌萎缩蛋白还有其他几种组织特异性异构体，有些仅在大脑或视网膜中表达，或主要在这些部位表达。影响这些组织特异性异构体正确表达的突变与DMD常见的中枢神经系统受累有关。罕见突变也导致等位基因疾病X连锁扩张型心肌病，其中抗肌萎缩蛋白的表达或功能主要或仅在心脏中受到影响。对肌营养不良症患者抗肌萎缩蛋白基因的基因型定义，让我们对该蛋白质本身的功能重要结构域有了很多了解，并为几种控制基因表达谱的调控机制提供了见解。在这里，我们重点关注目前对抗肌萎缩蛋白基因突变的基因型-表型关系的理解及其对基因功能的影响。
